This application addresses broad Challenge Area (04): Clinical Research, and specific Challenge Topic, 04- HL-104: Perform secondary analyses of existing data to answer important clinical and preventive medicine research questions. Atrial fibrillation (AF) is the most frequent cardiac arrhythmia in clinical practice. Epidemiologic studies have provided valuable information on risk factors for AF. These results, however, come from a limited set of cohorts of mostly white populations in the United States and Western Europe. Important knowledge gaps exist in our knowledge of AF epidemiology. First, the epidemiology of AF in non-white ethnic groups is not well defined. Second, little information exists on how changes in AF risk factors could affect the future risk of AF. Third, the role of inflammation, fibrosis, atrial stretch, myocardial injury and hemostasis in the incidence of AF is not appropriately understood. We propose to assess risk factors for AF in a bi-racial population, and explore novel risk factors and biomarkers of AF in the context of the Atherosclerosis Risk in Communities (ARIC) cohort. The ARIC cohort comprises a representative sample of 15,792 men and women (27% African-Americans) from 4 US communities examined in 1987-89, and followed up since then. Specifically, we will assess the following aims: (1) to evaluate whether previously described risk factors for AF in whites are associated with AF incidence in the ARIC African-American population and to describe whether changes in previously described risk factors affect the future risk of AF;(2) to study the role of novel cardiovascular risk factors in the incidence of AF. Specifically, we will evaluate biomarkers of inflammation, atrial stretch, myocardial injury, atrial fibrosis and remodeling, and hemostasis. At baseline and in 3 subsequent visits, participants underwent a physical exam, extensive risk factor ascertainment, and collection of blood samples. We will identify incident cases of AF through hospitalization discharges, ECGs conducted in the follow-up and data from Medicare claims, and measure biomarkers for fibrosis in a sample of the study population. A cohort or case-cohort approach, depending on the specific aim, will be used to evaluate the association between risk factors and biomarkers and the risk of AF. This proposal will provide novel information on risk factors for AF, particularly among African-Americans, will contribute decisively to our understanding of the ethiopathogenic processes underlying AF, and will help to inform potential preventive measures in high-risk populations. This proposal will provide new insights into the causes of atrial fibrillation. Particularly, we will try to disentangle the mechanisms explaining the lower incidence of atrial fibrillation in African-Americans, and identify new biomarkers for atrial fibrillation. Results of this proposal will inform development of new treatments and preventive measures for atrial fibrillation.